Solvent-free tetrahydropyranylation of alcoholscatalyzed by amine methanesulfonates

Rui Wang • MingZhu Sun • Heng Jiang

Received: 14 September 2010 / Accepted: 29 October 2010 / Published online: 24 November 2010

� Springer Science+Business Media B.V. 2010

Abstract A comparative study of tetrahydropyranylation of alcohols under

various solvents or solvent-free conditions using different amine methanesulfonates

as catalysts shows that tetrahydropyranyl ethers of alcohols are obtained under

solvent-free conditions in good yields using catalytic amounts of triethylenediamine

methanesulfonate, 1,6-hexanediamine methanesulfonate, diethylenetriamine meth-

anesulfonate and pyridine methanesulfonate, respectively. The reaction occurs

readily in short times at room temperature catalyzed by these catalysts, especially

triethylenediamine methanesulfonate. Some of the major advantages of this pro-

cedure are that the catalysts are environmentally friendly, highly effective, and easy

to prepare and handle. The reaction is also clean and needs no solvent, and the

work-up is very simple.

Keywords Methanesulfonates � Tetrahydropyranylation � Catalysts � Solvent-free �Alcohols � Protection

Introduction

Tetrahydropyranylation is an attractively protective method that is often used for

protection of alcohol moieties, in particular natural products, due to the remarkable

stability of tetrahydropyranyl (THP) ethers under various reaction conditions such

as strongly basic media, oxidation, reduction with hydride, reactions involving

R. Wang (&) � H. Jiang

School of Chemistry and Materials Science, Liaoning Shihua University, 113001 Fushun,

Liaoning, People’s Republic of China

e-mail: wr_wrwr@hotmail.com

M. Sun

School of Petrochemical Engineering, ShenYang University of Technology, 111003 Liaoyang,

Liaoning, People’s Republic of China

123

Res Chem Intermed (2011) 37:61–67

DOI 10.1007/s11164-010-0222-6

Grignard reagents and alkyllithiums [1]. Acid catalysts play a predominant role in

organic synthesis, in particular tetrahydropyranylation. Due to its ease of handling

and recovering, various solid acids were introduced, which include protic acids

[2, 3], Lewis acids [4, 5], ion exchange resins [6, 7], solid silica-based sulfonic acid

[8], zeolites [9, 10], hetropolyacids [11, 12], and clays [13, 14]. The main problems

associated with solid acids are the complicated preparation procedure, corrosive-

ness, the expense, the harsh reaction conditions, the need for solvents such as

CH2Cl2, as well as unsatisfactory product yields, etc. Therefore, for both

environmental and economical reasons, there is an ongoing effort to develop new

acid catalysts.

Methanesulfonic acid, which is a readily biodegradable and environmentally

friendly material [15], has been studied as an acid catalyst in esterification,

condensation, and alkylation reactions [16–18]. In our study, methanesulfonic acid,

used as a tetrahydropyranylation catalyst, has been found, like many strongly acidic

catalysts [19], to produce polymeric products of 3,4-dihydro-2H-pyran (DHP). In

recent years, methanesulfonates as catalysts have attracted great interest throughout

scientific communities [20–22]. This is mainly due to the distinct advantages such

as their non-toxicity, low cost, non-corrosiveness, and ease of preparation and

recovery. In this direction, we now wish to report amine methanesulfonates (AMS),

which acted as Brønsted acid, are excellent and effective catalysts for tetrahydro-

pyranylation of alcohols under mild conditions.

Experimental

General

The products were characterized by comparison of their physical data with those of

known samples. GC analysis was carried out on an Auto System XL series gas

chromatograph instrument from Perkin-Elmer. Fourier transform infrared (FTIR)

spectra were obtained on a Perkin-Elmer Spectrum GX. 1H NMR spectra were

recorded on Bruker AVANCE 600 spectrometer in CDCl3 using TMS as an internal

standard. Melting points were determined using RY-1 micromelting point

apparatus.

Typical procedure for preparation of AMS

Stoichiometric methanesulfonic acid and triethylenediamine with 2:1 M ratio were

mixed in an agate mortar at room temperature. After grinding for about 1–2 h, a

small amount of alcohol was added. The solid was filtered off and dried in an oven

at 353 K. The resultant salt (triethylenediamine methanesulfonate, TEDAMS) was

obtained. Using the above procedure, other AMS catalysts (Table 1) could also be

synthesized.

62 R. Wang et al.

123

General procedure for the tetrahydropyranylation of alcohols

Protection was carried out mixing the alcohol (20 mmol), 2.02 g DHP (24 mmol,

1.2 equiv.) and the stated quantity of TEDAMS (Table 3). The suspension was

stirred at room temperature, and the progress of the reaction was monitored by GC.

After completion of the reaction, the mixture was diluted with benzene (10 ml). The

catalyst was filtered off and then washed with benzene (2 9 10 ml). The filtrate was

washed with 1 M NaOH and then dried over anhydrous Na2SO4 and evaporated.

Further purification was achieved by column chromatography on silica gel to obtain

the corresponding THP ether.

Results and discussion

Tetrahydropyranylation reactions of alcohols were catalyzed by a variety of AMS

under similar reaction conditions. The results of the tetrahydropyranylation of benzyl

alcohol are summarized in Table 1. The protection methodology using the above AMS

(Table 1, entries 1–4) as catalysts is successful and gives satisfactory yields.

Table 1 Comparison the activity of various catalysts in the tetrahydropyranylation of benzyl alcohol

under solvent-free conditions

O Solvent-Free, r.t.

AMSCH2OH

OOCH2

Entry Catalysts Time/h Yield/%a

1 [CH3SO3] HN NH[CH3SO3]

0.2 94

2 [CH3SO3] H3N(CH2)6NH3 [CH3SO3] 0.2 93

3 [CH3SO3] H3N(CH2)2

[CH3SO3] H3N(CH2)2NH2[CH3SO3]

6 90

4NH [CH3SO3]

4.5 91

5CH3 NH3[CH3SO3]

3 2

6Cl NH3[CH3SO3]

3 2

7

C NH2[CH3SO3]

CH3

CH32

3 2

Benzyl alcohol (20 mmol), DHP (24 mmol), catalyst (0.8 mmol)a Yields based on the isolated products

Solvent-free tetrahydropyranylation of alcohols 63

123

Moreover, a vigorous reaction takes place in the presence of a catalytic amount of

p-toluidine methanesulfonate (Table 1, entry 5), resulting in the formation of a deep

reddish brown viscous liquid (probably resulting from the polymerization of

dihydropyran). The yield of the corresponding tetrahydropyranyl ether from this

reaction mixture is very low and most of the alcohol remains unreacted. The same

thing also takes place when 4,40-bis (a, a-dimethylbenzyl) diphenylamine methane-

sulfonate and p-chloroaniline methanesulfonate (Table 1, entries 6–7) are utilized to

protect alcohols in the same reaction conditions. The possible reason for this is that

their (Table 1, entries 5–7) acidity is stronger than the others’ (Table 1, entries 1–4).

Among the described AMS catalysts, the activities of TEDAMS (Table 1, entry 1)

and 1,6-hexanediamine methanesulfonate (Table 1, entry 2), especially TEDAMS

(Table 1, entry 1), are superior to the others’. Investigation of applications of

TEDAMS (Table 1, entry 1) and 1,6-hexanediamine methanesulfonate [23] (Table 1,

entry 2) as highly active catalysts is of practical importance.

In order to optimize the reaction conditions, we attempted the conversion of

benzyl alcohol (20 mmol) to the corresponding THP ether with different amount of

DHP and TEDAMS (0.8 mmol) under various solvents and solvent-free conditions

at room temperature. The results (Table 2) indicate that the yield of the

tetrahydropyranylation reaction of benzyl alcohol with DHP (molar ratio 1:1.2)

under solvent-free condition is higher and the reaction time is shorter.

Several examples illustrating this novel and rapid procedure for tetrahydropyr-

anylation of alcohols using TEDAMS as catalyst under the optimal condition are

presented in Table 2. Isomeric alcohol (Table 3, entries 4, 8, 10, 12), aromatic

alcohol (Table 3, entries 15, 16), furfuryl alcohol (Table 3, entry 18) and optically

active alcohol (-)-menthol (Table 3, entry 19) by using TEDAMS undergo facile

tetrahydropyranylation to form THP ethers in good to excellent yields. Notably, the

increase of carbon number in primary alcohols (Table 3, entries 1–3, 5, 9, 11, 13,

Table 2 Tetrahydropyranylation of benzyl alcohol under different condition using TEDAMS as catalyst

O

CH2OH [CH3SO3] HN NH[CH3SO3]

OOCH2

Entry nbenzyl alcohol : nDHP Solventsa Time/h Yield/%b

1 1:1.1 Benzene 0.5 87

2 1:1.1 None 0.5 89

3 1:1.2 Benzene 0.5 87

4 1:1.2 Tetrahydrofuran 0.6 91

5 1:1.2 Dichloromethane 0.8 91

6 1:1.2 None 0.2 94

7 1:1.3 Benzene 0.5 91

8 1:1.3 None 0.3 94

a The reaction was carried out in 10 ml of solventb Yields based on the isolated products

64 R. Wang et al.

123

14) decreases the yields of THP ethers. The protection of secondary alcohol

(Table 3, entry 6), tertiary alcohol (Table 3, entry 7), and cyclic saturated alcohol

(Table 3, entry 17) afforded the corresponding THP ethers in low yields at long

reaction time in the same conditions. The absence of by-product obtained by GC

analysis shows the high selectivity of TEDAMS catalyst.

Based on our results, the plausible mechanism for the protection of alcohols is

shown in scheme 1. It is assumed that DHP protonated with Brønsted acid sites of

TEDAMS. The intermediate product further reacts with alcohol to give corre-

sponding THP ether.

Conclusions

In conclusion, tetrahydropyranylation of alcohols has been carried out successfully

using the new AMS catalyst, specifically TEDAMS. High effectivity and easy of

Table 3 TEDAMS catalyzed tetrahydropyranylation of alcohols under solvent-free conditions

[CH3SO3] HN NH[CH3SO3]

Solvent-Free, r.t.OR OH

O OR

Entry Alcohols Cat: DHP (mmol: mmol) Time/h Yield/%a Refs.b

1 CH3OH 0.8:24 0.5 93 [24]

2 C2H5OH 0.8:24 0.5 93 [24]

3 n-C3H7OH 2:24 2 90 [24]

4 i-C3H7OH 0.8:24 2.5 80 [13]

5 n-C4H9OH 1.3:24 1.3 89 [24]

6 s-C4H9OH 2:24 7 78 [13]

7 t-C4H9OH 2:24 10 69 [25]

8 i-C4H9OH 1.3:24 1 90 [13]

9 n-C5H11OH 1.3:24 2 88 [26]

10 (CH3)2CHCH2CH2OH 1.3:24 1 93 [13]

11 n-C8H17OH 2:24 2 85 [13]

12 i-C8H17OH 0.8:24 1.5 91 [13]

13 n-C12H25OH 2:24 4.5 77 [13]

14 n-C16H33OH 2:24 14 80 [5]

15 PhCH2OH 0.8:24 0.2 94 [13, 24]

16 PhCH2CH2OH 0.8:24 0.3 94 [27]

17 c-C6H11OH 2:24 5 79 [13, 19]

18 Furfuryl alcohol 0.8:24 1 90 [13, 24]

19 (-)-menthol 1.3:24 1 86 [28]

a Yields based on the isolated pure products and confirmed by comparison with authentic samples (GC,

IR and 1H NMR)b References for spectroscopic data of products

Solvent-free tetrahydropyranylation of alcohols 65

123

preparation and handling of the catalyst with its environmentally friendly nature

should make the method particularly attractive. Most importantly, work-up

procedures in our study have been simplified due to the absence of solvent.

Because of the outstanding advantages, this method is expected to have wide

applicability for the protection of various hydroxyl compounds.

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